This study was aimed at the elucidation of mechanisms and the identification of early paramaters of immune dysfunction in SIV induced primate AIDS. The results obtained on disease susceptible rhesus macaques experimentally with SIVmac251 were compared to parameters derived from naturally infected disease resistant sooty mangabey monkeys. A total of 9 macaques were immunized with keyhole limpet hemocyanin (KLH), tetanus toxoid (TT) and the highly attenuated influenza virus strain A/PR8 prior to challenge with SIVmac251 (6 out of the 9 macaques). Immune responses not only to SIV but also to KLH, TT and influenza were followed throughout the course of infection in order to identify the onset of critical immune dysfunctions following SIV infection. Data accumulated so far, suggest that a rapid loss of antigen specific IFN? response is observed in all SIV infected macaques accompanied with a gradual increase in IL-6 response as the monkeys reach the clinically symptomatic s tage. Humoral responses established prior to SIV infection did not seem to be affected when compared to uninfected control animals. However, the kinetic of cell mediated response to influenza and the capacity of the animal's to synthesize IL-2 in response to antigenic stimulation in vitro, appeared to correlate with the length of time between infection with SIV and development of AIDS, suggesting a preponderant role for these mechanisms at controlling lentiviral infection.